μL Min Research Articles

Capillarity Enabled Large-Array Liquid Metal Electrodes for Compact and High-Throughput Dielectrophoretic Microfluidics.

Dielectrophoresis (DEP) particle separation has label-free, well-controllable, and low-damage merits. Sidewall microelectrodes made of liquid metal alloy (LMA) inherits the additional advantage of thick electrodes to generate impactful DEP force. However, existing LMA electrode-based devices lack the ability to integrate large-array electrodes in a compact footprint, severely limiting flow rate and thus throughput. Herein, a facile and versatile method is proposed to integrate high-density thick LMA electrodes in microfluidic devices, taking advantage of the passive control ability of capillary burst valves (CBVs). CBVs with carefully designed burst pressures are co-designed in microfluidic channels, allowing self-assembly of LMA electrode array through simple hand-push injection. The arrayed electrode configuration brings the accumulative DEP deflection effect. Specifically, The fabricated 5000 pairs of sidewall electrodes in a compact chip are demonstrted to achieve ten times higher throughput in DEP deflection. The 5000-electrode-pair device is applied to successfully separate four mixed samples, including human peripheral blood mononuclear cells and A549 cellswith the flow rate of 70 µL min-1. It is envisioned that this work can greatly facilitate LMA electrode array fabrication and offer a robust and versatile platform for DEP separation applications.

A liquid–metal-based microscale calorimetric in-chip flow sensor for flow rate measuring

Abstract This work proposes a liquid–metal-based calorimetric micro-flow sensor within a polydimethylsiloxane (PDMS) chip. It can measure the flow rate of fluid in microscale channels, with a range as low as several microliters per minute. This in-chip sensor is proposed to solve the issue of detecting the flow rate in microfluidic systems. To make the sensor compatible with PDMS microfluidic chips, low-melting-point gallium-based alloy and bismuth-based (bi-based) alloy are used to make the micro heater and bi-metal thermocouples, for these alloys can be easily injected into a PDMS chip to form electrodes. To minimize heat resistance (or temperature difference) between fluid and the detecting ends of thermocouples, these ends are directly exposed to liquid in the flow channel with the help of a special reversible bonding technology. Thermocouples are connected in series to improve the sensor’s response. A novel method to bond and electrically connect the sensor to a print circuit board is also elaborated. Since the calorimetric flow sensor is sensitive to heating power, fluid temperature and environment cooling, a dimensionless parameter less independent of these factors is deduced from heat transfer theory, and this idea is used in result processing to offset the bad effect. Experiments with pure water show that this sensor can be used to detect flow rates, with a resolution up to 4 µl min−1 mV−1 and a range of 12 µl min−1 in this case, and that at different heating powers, the thermal potential results vary significantly whereas the dimensionless results nearly keep the same. Present work indicates that this sensor has the potential to be integrated into a PDMS microfluidic system and to provide accurate and stable results if a dimensionless method is used in data processing.

Higher Brain Uptake of Gentamicin and Ceftazidime under Isoflurane Anesthesia Compared to Ketamine/Xylazine.

We have recently shown that the volatile anesthetics isoflurane and sevoflurane acutely enhance the brain uptake of the hydrophilic markers sucrose and mannitol about two-fold from an awake condition, while the combined injection of the anesthetic agents ketamine and xylazine has no effect. The present study investigated two small-molecule hydrophilic drugs with potential neurotoxicity, the antibiotic agents ceftazidime and gentamicin. Transport studies using an in vitro blood-brain barrier (BBB) model, a monolayer of induced pluripotent stem cell-derived human brain microvascular endothelial cells seeded on Transwells, and LC-MS/MS analysis demonstrated the low permeability of both drugs in the range of sucrose, with permeability coefficients of 6.62 × 10-7 ± 2.34 × 10-7 cm/s for ceftazidime and 7.38 × 10-7 ± 2.29 × 10-7 cm/s for gentamicin. In vivo brain uptake studies of ceftazidime or gentamicin after IV doses of 25 mg/kg were performed in groups of 5-6 mice anesthetized at typical doses for surgical procedures with either isoflurane (1.5-2% v/v) or ketamine/xylazine (100:10 mg/kg I.P.). The brain uptake clearance, Kin, for ceftazidime increased from 0.033 ± 0.003 μL min-1 g-1 in the ketamine/xylazine group to 0.057 ± 0.006 μL min-1 g-1 in the isoflurane group (p = 0.0001), and from 0.052 ± 0.016 μL min-1 g-1 to 0.101 ± 0.034 μL min-1 g-1 (p = 0.0005) for gentamicin. We did not test the dose dependency of the uptake, because neither ceftazidime nor gentamicin are known substrates of any active uptake or efflux transporters at the BBB. In conclusion, the present study extends our previous findings with permeability markers and suggests that inhalational anesthetic isoflurane increases the BBB permeability of hydrophilic small-molecule endobiotics or xenobiotics when compared to the injection of ketamine/xylazine. This may be of clinical relevance in the case of potential neurotoxic substances.

High-Speed Schlieren Imaging of Vapor Formation in Electrospray Plume.

Previous mechanistic descriptions of electrosprays mostly focused on the dynamics of Taylor cones, initial droplets, and progeny droplets. However, vapor formation during droplet desolvation in an electrospray plume has not been discussed to a great extent. Here, we implement a double-pass on-axis schlieren high-speed imaging system to observe generation and propagation of vapors in an offline electrospray source under different conditions. Switching between turbulent and laminar vapor flow was observed for all of the scanned conditions, which may be attributed to randomly occurring disturbances in the sample flow inside the electrospray emitter. Calculation of mean vapor flow velocity and analysis of vapor flow patterns were performed using in-house developed image processing programs. Experiments performed at different electrospray voltages (0-6 kV), solvent flow rates (100-600 μL min-1), and methanol concentrations (50-100%), indicate only a weak dependency between electrospray voltage and mean vapor velocity, implying that the vapor is mostly neutral; thus, the vapor is not accelerated by electric field. On the other hand, electrospraying solutions of analytes (with mass 151 Da or 12 kDa) did not remarkably increase the overall vapor flow velocity. The source of vapor's velocity is attributed to the inertia of the electrospray droplets. Although there are some differences between a modern electrospray ionization (ESI) setup and the setup used in our experiment (e.g., using a higher flow rate and larger emitter), we believe the findings of our study can be projected to a modern ESI setup.

Interaction of Staphylococcus aureus and Candida albicans with surface-modified silica studied by ultra-high frequency acoustic wave biosensor.

In this work the bacteria S. aureus and fungi C. albicans were allowed to interact with quartz-based biosensor devices under different flow rates, with and without an anti-fouling coating. These experiments were conducted in order to determine if the level of fouling observed was affected by the flow rate. The biosensor used was an ultra-high frequency acoustic wave device (EMPAS) for investigation of device surface initial interaction of S. aureus or C. albicans under flow of PBS buffer at flow rates between 50 and 200 μL min-1. Surface-bound microbes were also visualized by fluorescence microscopy following these experiments. S. aureus bacteria was able to foul the bare quartz sensors at each flow rate tested, with the greatest degree of fouling observed at a flow rate of 100 μL min-1. C. albicans showed far less fouling of bare devices with the maximum fouling observed at a flow rate of 75 μL min-1. Antifouling MEG-OH coated sensors showed greatly reduced fouling for S. aureus, with between a 90 and 99% reduction in observed frequency change depending on the flow rate used, and between 22 and 90% for C. albicans. Fluorescence images of the microbes following the experiments correlated well with the frequency data, showing a marked decrease in the amount of bacteria seen on MEG-OH-coated surfaces compared to controls.

Portable platform for leukocyte extraction from blood using sheath-free microfluidic DLD.

Leukocyte count is routinely performed for diagnostic purposes and is rapidly emerging as a significant biomarker for a wide array of diseases. Additionally, leukocytes have demonstrated considerable promise in novel cell-based immunotherapies. However, the direct retrieval of leukocytes from whole blood is a significant challenge due to their low abundance compared to erythrocytes. Here, we introduce a microfluidic-based platform that isolates and recovers leukocytes from diluted whole blood in a single step. Our platform utilizes a novel, sheathless method to initially sediment and focus blood cells into a dense stream while flowing through a tubing before entering the microfluidic device. A hexagonal-shaped structure, patterned at the device's inlet, directs all the blood cells against the channel's outer walls. The focused cells are then separated based on their size using the deterministic lateral displacement (DLD) microfluidic technique. We evaluated various parameters that could influence leukocyte separation, including different focusing structures (assessed both computationally and experimentally), the orientation of the tubing-chip interface, the effects of blood sample hematocrit (dilution), and flow rate. Our device demonstrated the ability to isolate leukocytes from diluted blood with a separation efficiency of 100%, a recovery rate of 76%, and a purity of 80%, while maintaining a cell viability of 98%. The device operates for over 30 min at a flow rate of 2 μL min-1. Furthermore, we developed a handheld pressure controller to drive fluid flow, enhancing the operability of our platform outside of central laboratories and enabling near-patient testing. Our platform can be integrated with downstream cell-based assays and analytical methods that require high leukocyte purity (80%), ranging from cell counting to diagnostics and cell culture applications.

A simple and cost-effective hybrid stationary phase for the separation of peptides, proteins and benzene derivatives through liquid chromatography.

A very simple and cost-effective silica-based hybrid stationary phase was synthesized for the separation of five synthetic peptides, five proteins, and benzene derivatives. Silica monolith was synthesized via sol-gel process. Particles obtained through the grinding of silica monolith were suspended in methanol and sedimented under gravity to obtain sub-2 μm particles. A hybrid LC stationary phase was obtained by coating an ethylene glycol dimethacrylate co-polymer onto the particles via RAFT polymerization. The resultant stationary phase was characterized using SEM, FTIR, BET, and EDX analysis. A stainless steel column (200 mm long × 0.2 mm ID) was packed with the resultant stationary phase via pressure tapering protocol using a slurry packing machine. The column resulted in the average number of theoretical plates/meter (287 500 for synthetic peptides, 276 800 for proteins, and 226 100 for benzene derivatives) under the elution conditions of acetonitrile/50 mM ammonium format (68/32 v/v%) with a flow rate of 0.785 μL min-1. Since the column resulted in the separation of synthetic peptides, proteins, and benzene derivatives with very good chromatographic performance, it could possibly separate any complex mixture of peptides and proteins with better chromatographic performance.

Small extracellular vesicles' enrichment from biological fluids using an acoustic trap.

Small extracellular vesicles (sEVs), a form of extracellular vesicles, are lipid bilayered structures released by all cells. Large-scale studies on sEVs from clinical samples are necessary, but a major obstacle is the lack of rapid, reproducible, efficient, and low-cost methods to enrich sEVs. Acoustic microfluidics have the advantage of being label-free and biocompatible, which have been reported to successfully enrich sEVs. In this paper, we present a highly efficient acoustic microfluidic trap that can offer low and large volume compatible ways of enriching sEVs from biological fluids by flexible structure design. It uses the idea of pre-loading larger seed particles in the acoustic trap to enable sub-micron particle capturing. The microfluidic chip is actuated using a piezoelectric plate transducer attached to a silicon-glass bonding plate with circular cavities. Each cavity works as a resonant unit, excited at the frequency of both the half wave resonance in the main plane and inverted quarter wave resonance in the depth direction, which has the ability to strongly trap seed particles at the center, thereby improving the subsequent nanoparticle capture efficiency. Mean trapping efficiencies of 35.62% and 64.27% were obtained using 60 nm and 100 nm nanobeads, respectively. By the use of this technology, we have successfully enriched sEVs from cell culture conditioned media and blood plasma at a flow rate of 10 μL min-1. The isolated sEV subpopulations are characterized by NTA and TEM, and their protein cargo is determined by WB. This acoustic trapping chip provides a rapid and robust method to enrich sEVs from biofluids with high reproducibility and sufficient quantities. Therefore, it can serve as a new tool for biological and clinical research such as cancer diagnosis and drug delivery.

Aptamer-based biotherapeutic conjugate for shear responsive release of Von Willebrand factor A1 domain.

Smart polymers that mimic and even surpass the functionality of natural responsive materials have been actively researched. This study explores the design and characterization of a Single-MOlecule-based material REsponsive to Shear (SMORES) for the targeted release of A1, the platelet binding domain of the blood clotting protein von Willebrand factor (VWF). Each SMORES construct employs an aptamer molecule as the flow transducer and a microparticle to sense and amplify the hydrodynamic force. Within the construct, the aptamer, ARC1172, undergoes conformational changes beyond a shear stress threshold, mimicking the shear-responsive behavior of VWF. This conformational alteration modulates the bioavailability of its target, the VWF-A1 domain, ultimately releasing it at elevated shear. Through optical tweezer-based single-molecule force measurement, ARC1172s role as a force transducer was assessed by examining its unfolding under constant pulling force. We also investigated its refolding rate as a function of force under varied relaxation periods. These analyses revealed a narrow range of threshold forces (3-7 pN) governing the transition between folded and unfolded states. We subsequently constructed the SMORES material by conjugating ARC1172 and a microbead, and immobilizing the other end of the aptamer on a substrate. Single-molecule flow experiments on immobilized SMORES constructs revealed a peak A1 domain release within a flow rate range of (40-70 μL min-1). A COMSOL Multiphysics model translated these flow rates to total forces of 3.10 pN-5.63 pN experienced by the aptamers, aligning with single-molecule force microscopy predictions. Evaluation under variable flow conditions showed a peak binding of A1 to the platelet glycoprotein Ib (GPIB) within the same force range, confirming released payload functionality. Building on knowledge of aptamer biomechanics, this study presents a new strategy to create shear-stimulated biomaterials based on single biomolecules.

Grease the gears: how lubrication of syringe pumps impacts microfluidic flow precision.

Pumps are indispensable for analytical applications and ensure controlled fluid movement. Syringe pumps are among today's most prevalent liquid delivery systems, especially for high-pressure, stable, low-flow-rate microfluidic applications. Due to moving mechanical parts of the assembly, regular maintenance is essential to ensure reliable operation and flow rates. However, lubrication of the mechanics is easily overlooked because the research focuses on novel analytical applications rather than on the maintenance of pumps. Here, we investigate the lubrication of the syringe pump guide rods with its effect on the flow rate stability after regular pump cleaning from contaminations. The guide rods of syringe pumps were thoroughly cleaned from any lubricant, and the flow rate for specified flowrates between 5 and 100 μL min-1 was measured, revealing tremendous flow rate fluctuations with a coefficient of variation (CV) value up to 0.34. In contrast, flow rate measurements of syringe pumps with lubricated guide rods show a five-fold smoother flow rate fluctuation depending on the specified flow rate with CV values below 0.07. These differences in flow rate's CV were most significant for pressure drops below 500 mbar, relevant for many lab-on-a-chip applications. In summary, we emphasize the awareness of lubricating moving parts of syringe pumps to achieve constant flow rates, minimize wear, and ensure the reliable operation of, for instance, accurate lab-on-a-chip workflows.

A multi-channel microfluidic platform based on human flavin-containing monooxygenase 3 for personalised medicine.

Human flavin-containing monooxygenase 3 (FMO3) is a drug-metabolizing enzyme (DME) which is known to be highly polymorphic. Some of its polymorphic variants are associated with inter-individual differences that contribute to drug response. In order to measure these differences, the implementation of a quick and efficient in vitro assay is highly desirable. To this end, in this work a microfluidic immobilized enzyme reactor (μ-IMER) was developed with four separate serpentines where FMO3 and its two common polymorphic variants (V257M and E158K) were covalently immobilized via glutaraldehyde cross-linking in the presence of a polylysine coating. Computational fluid dynamics simulations were performed to calculate the selected substrate retention time in serpentines with different surface areas at various flow rates. The oxidation of tamoxifen, an anti-breast cancer drug, was used as a model reaction to characterize the new device in terms of available surface area for immobilization, channel coating, and applied flow rate. The highest amount of product was obtained when applying a 10 μL min-1 flow rate on polylysine-coated serpentines with a surface area of 90 mm2 each. Moreover, these conditions were used to test the device as a multi-enzymatic platform by simultaneously assessing the conversion of tamoxifen by FMO3 and its two polymorphic variants immobilized on different serpentines of the same chip. The results obtained demonstrate that the differences observed in the conversion of tamoxifen within the chip are similar to those already published (E158K > WT > V257M). Therefore, this microfluidic platform provides a feasible option for fabricating devices for personalised medicine.

Electrostatic-hydraulic coupled soft actuator for micropump application

The development of a soft actuator with high displacement is crucial for the effective operation of micropumps, ensuring a high fluid pump rate. This study introduces an innovative approach by presenting the design and fabrication of a novel electrostatic-hydraulic coupled soft actuator for a micropump within a microfluidic system. This pioneering soft actuator, leveraging electrostatic-hydraulic coupling, showcases a unique solution to enhance the performance of micropumps. The versatility of such a soft actuator makes it particularly promising for biomedical applications. The actuator comprises dielectric fluid in an elastomeric shell and electrodes to form the out-of-plane fluid-amplified displacement. This displacement amplification was used to generate a pumping actuation in the micropump. The actuator was characterized in terms of dielectric fluid volume, electrode size, temporal response, and amplification displacement. The soft actuator showed a maximum amplified displacement of 0.51 mm at 10 kV of the applied voltage, but a higher voltage caused a dielectric breakdown. Moreover, the actuator demonstrated the ability to operate at frequencies of 0.25 Hz and 0.1 Hz. The results of the study indicate that the fabricated electrostatic-hydraulic coupled soft actuator is a dependable and effective method of actuation for a micropump in a microfluidic system. The experimental characterization of the micropump revealed a maximum flow rate of 2304 μl min−1.

Nanogram-scale boron isotope analysis through micro-distillation and Nu Plasma 3 MC-ICP-MS

The determination of boron isotopes (δ11B) represents a powerful tool for a variety of applications such as the reconstruction of past ocean pH and atmospheric pCO2 from the analysis of marine biogenic carbonates. In recent years, MC-ICP-MS has gained popularity over other techniques thanks to its superior sample throughput and high ionization efficiency. This study evaluates, for the first time, the performance of the Nu Instruments Plasma 3 MC-ICP-MS for measuring δ11B using different sample introduction systems and detector configurations. The main goal is to provide a detailed methodology for nanogram-scale boron isotope analysis through a straightforward approach that can be easily adopted. Boron (B) purification from the carbonate matrix was performed through micro-distillation, using a temperature of 95 °C and a minimum heating duration of 15 h, allowing the full recovery of B from up to 3 mg of carbonate mass. We attained blank values (on average 14 ± 6 pg, 1 SD, n = 27) comparable to the lowest micro-distillation blanks reported in the literature. Three sample introduction systems were tested, and the 30 μL min−1 nebuliser system outperformed the 50 and 170 μL min−1 systems in terms of signal intensity per mass of B. Two detector configurations were used based on the total boron signal intensity achieved: (1) FC11/FC12, with two Faraday cups fitted to 1011 Ω and 1012 Ω amplifier resistors to detect 11B and 10B ion beams, respectively, and (2) FC12/IC, with which we investigated, for the first time, the feasibility of combining an ion counter for detecting 10B, and a Faraday cup fitted to a 1012 Ω amplifier for 11B. The FC12/IC configuration provided accurate results compared to the use of two Faraday cups for total boron signals lower than 0.35 V (∼12 ng of B in the analysed solution). The proposed analytical procedure was validated through the analysis of several reference materials with varying boron amounts, including clam JCt-1, coral JCp-1, NIST RM 8301 Foram and Coral solutions, and boric acid ERM-AE121. Furthermore, the long-term reproducibility was assessed with two in-house standards (coral CLD-1 and foraminifera GINF-1), providing values of 25.68 ± 0.23 ‰ (2SD, n = 53; with 14–36 ng of B) and 14.90 ± 0.16 ‰ (2SD, n = 12; with 11–16 ng of B), respectively.

Ciprofol is primarily glucuronidated by UGT1A9 and predicted not to cause drug-drug interactions with typical substrates of CYP1A2, CYP2B6, and CYP2C19

Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown. This study systematically characterized UGTs that contribute to the formation of M4 using human liver microsomes (HLM), human intestinal microsomes (HIM), and human recombinant UGTs. The inhibitory potential of ciprofol and M4 against major human UGTs and cytochrome P450 enzymes (P450s) was also explored. In vitro-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) simulations were performed to predict potential in vivo drug-drug interactions (DDIs) caused by ciprofol. Glucuronidation of ciprofol followed Michaelis-Menten kinetics in both HLM and HIM with apparent Km values of 345 and 412 μM, Vmax values of 2214 and 444 nmol min−1·mg protein−1, respectively. The in vitro intrinsic clearances (CLint = Vmax/Km) for ciprofol glucuronidation by HLM and HIM were 6.4 and 1.1 μL min−1·mg protein−1, respectively. Human recombinant UGT studies revealed that UGT1A9 is the predominant isoform mediating M4 formation, followed by UGT1A7, with UGT1A8 playing a minor role. Ciprofol competitively inhibited CYP1A2 (Ki = 12 μM) and CYP2B6 (Ki = 4.7 μM), and noncompetitively inhibited CYP2C19 (Ki = 29 μM). No time-dependent inhibition by ciprofol was noted for CYP1A2, CYP2B6, or CYP2C19. In contrast, M4 showed limited or no inhibitory effects against selected P450s. Neither ciprofol nor M4 inhibited UGTs significantly. Initial IVIVE suggested potential ciprofol-mediated inhibition of CYP1A2, CYP2B6, and CYP2C19 inhibition in vivo. However, PBPK simulations showed no significant effect on phenacetin, bupropion, and S-mephenytoin exposure or peak plasma concentration. Our findings are pertinent for future DDI studies of ciprofol as either a perpetrator or victim drug.

Effective transformation of hydrothermally grown TiO2 nanorods to nanotube arrays for improved PEC hydrogen evolution

Innovative green and renewable energy solutions to achieve carbon neutrality could be achieved using advanced functional materials. For the commercial realization of PEC water-splitting technology, low-cost, high active surface area, and high-performance catalyst is required. To do so, engineering the structure of the catalyst, controlling morphology and synthesis method becomes essential. So herein insightful design of experiments was carried out to synthesize in-situ growth of facet-controlled, vertically oriented rutile titanium dioxide (TiO2) nanorod (TNR) arrays and subsequent conversion to nanotubes (TNT) arrays using a facile hydrothermal approach. The photoelectrochemical (PEC) measurements at 1.23 V vs. RHE reveal a high photocurrent density of 976.8 µA cm−2 and a high theoretical H2 production of 7.4 µl min−1 cm−2 for FTO-grown TNTs. The increased exposed active surface area, improved light penetration, and uniformly oriented structures are responsible for higher response of TNTs over TNRs. Thus, present study offers a one-step conversion of nanorods to nanotubes and the corresponding improvement in PEC performances.

SLC22A11 Inserts the Uremic Toxins Indoxyl Sulfate and P-Cresol Sulfate into the Plasma Membrane.

Chronic kidney disease (CKD) is a global health concern affecting millions worldwide. One of the critical challenges in CKD is the accumulation of uremic toxins such as p-cresol sulfate (pCS) and indoxyl sulfate (IS), which contribute to systemic damage and CKD progression. Understanding the transport mechanisms of these prominent toxins is essential for developing effective treatments. Here, we investigated whether pCS and IS are routed to the plasma membrane or to the cytosol by two key transporters, SLC22A11 and OAT1. To distinguish between cytosolic transport and plasma membrane insertion, we used a hyperosmolarity assay in which the accumulation of substrates into HEK-293 cells in isotonic and hypertonic buffers was measured in parallel using LC-MS/MS. Judging from the efficiency of transport (TE), pCS is a relevant substrate of SLC22A11 at 7.8 ± 1.4 µL min-1 mg protein-1 but not as good as estrone-3-sulfate; OAT1 translocates pCS less efficiently. The TE of SLC22A11 for IS was similar to pCS. For OAT1, however, IS is an excellent substrate. With OAT1 and p-aminohippuric acid, our study revealed an influence of transporter abundance on the outcomes of the hyperosmolarity assay; very high transport activity confounded results. SLC22A11 was found to insert both pCS and IS into the plasma membrane, whereas OAT1 conveys these toxins to the cytosol. These disparate transport mechanisms bear profound ramifications for toxicity. Membrane insertion might promote membrane damage and microvesicle release. Our results underscore the imperative for detailed structural inquiries into the translocation of small molecules.

Enhancing liquid phase microextraction enrichment in microchip devices under semi-stagnant conditions

Liquid-phase microextraction (LPME) in microfluidic devices involves extraction of acids or bases by diffusion in a pH gradient, from aqueous sample, through a supported liquid membrane (SLM), and into aqueous acceptor phase. The SLM is an integrated part of the device, and separates the donor (sample) and acceptor phase channels. In this work, the geometry of the donor and acceptor phase channels were studied and optimized. With optimal channel geometry (12 mm length, 2 mm width, 0.12 mm depth), metoprolol, haloperidol, nortriptyline, and loperamide were extracted from 900 μL urine and into 25 μL stagnant 10 mM HCl using a mixture of dihexyl ether and tributyl phosphate 1:1 v/v as the SLM. During 30 min of extraction, where the sample was pumped into the system at 30 μL min−1 and the acceptor phase was stagnant, recoveries exceeded 75 % and enrichment factors up to 28 were obtained. Evaluation of the analytical performance supported the reliability of the device in combination with HPLC-UV detection. Implementation of LPME in microfluidic devices is expected to increase in the future and the current paper provides experimental support for the importance of the careful design of the donor and acceptor channels.

Self-catalytic nickel hollow fiber membrane reactor for hydrogen production via toluene steam reforming

Metal-nickel membrane exhibits good H2 separation performance and inherent catalytic activity, making it a promising candidate as a membrane reactor in the simultaneous catalytic reforming of hydrocarbons and H2 separation. In this work, nickel hollow fiber membranes were fabricated using a spinning/sintering technology and subsequently employed in a membrane reactor for toluene steam reforming and H2 separation. The catalytic H2 production and permeation performance of the toluene steam reforming (TSR) hollow fiber membrane reactor were investigated under varying conditions, such as temperature, feed flow rate, steam-to-carbon ratio (S/C). The results show that toluene can be fully converted with a toluene feed flow rate of 1.5 μL min−1. Increasing S/C can enhance the H2 production, but excessive steam will lead to a decrease of the H2 permeation flux. The H2 yield and H2 permeation flux are 24.2% and 4.35 mmol m−2 s−1, respectively, under the conditions of S/C = 3, Ar = 90 mL min−1 and N2 = 3 mL min−1 at a temperature of 950 °C. The H2 yield and H2 permeation flux of the TSR membrane reactor did not significantly decrease within 96 h. In addition, the membrane reactor can operate stably within 62 h in an atmosphere containing 1000 ppm H2S.

Determination of psychoactive substances in one microliter plasma using a novel 3D printing microfluidic paper-based column coupled to liquid chromatography-mass spectrometry

Paper spray ionization is a simple method to analyze samples by mass spectrometry (MS) without sample preparation. However, using paper substrates results in limited performance due to low lifetime, low reproducibility, severe analyte diffusion, and poor chromatography. To address these issues, a stereolithography 3D printed microfluidic paper-based column coupled to liquid chromatography-MS (µPC-LC-MS) was developed. The fabrication process created well-defined microchannels inside a single paper substrate in less than 1 s. The µPC-LC-MS significantly extended the lifetime of the substrate, up to 50 min per run with continuous gradient elution at a flow rate of 20 µL min-1 from regular LC pumps. A single µPC can be reused up to 5 cycles with an RSD of 9.5 % without signal reduction, overloading, or interference. Separation of three psychoactive substances/metabolites (methamphetamine, 7-aminonitrazepam, and morphine-3-glucuronide) was achieved with peak resolution from 0.50 to 1.21, high sensitivity (LOD between 0.5 and 1 ng mL-1) and accuracy (87.0–109.1 %), linearity from 5 to 500 ng mL-1 in both water and plasma, and coefficient of determination (R2) from 0.993 to 1.000 using only 1 µL plasma. The µPC-LC-MS demonstrated robustness and sensitivity, making it a promising tool for bioanalysis based on paper-based microfluidics.

Perspiration permeable, textile embeddable microfluidic sweat sensor

Epidermal microfluidic devices are continuously being developed for efficient sweat collection and sweat rate detection. However, most microfluidic designs ignore the use of airtight/adhesive substrate will block the natural perspiration of the covered sweat pores, which will seriously affect normal sweat production and long-term wearable comfort. Herein, we present a Janus textile-embedded microfluidic sensor platform with high breathability and directional sweat permeability for synchronous sweat rate and total electrolyte concentration detection. The device consists of a hollowed-out serpentine microchannel with interdigital electrodes and Janus textile. The dual-mode signal of the sweat rate (0.2–4.0 μL min−1) and total ionic charge concentration (10–200 mmol L−1) can be obtained synchronously by decoupling conductance step signals generated when sweat flows through alternating interdigitated spokes at equal intervals in the microchannel. Meanwhile, the hollowed-out microchannel structure significantly reduces the coverage area of the sensor on the skin, and the Janus textile-embedded device ensures a comfortable skin/device interface (fewer sweat pores are blocked) and improves breathability (503.15 g m−2 d−1) and sweat permeability (directional liquid transportation) during long-term monitoring. This device is washable and reusable, which shows the potential to integrate with clothing and smart textile, and thus facilitate the practicality of wearable sweat sensors for personalized healthcare.